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A Cretaceous/Paleogene (K/Pg) boundary interval in the north flank of Alborz Mountains (Aboksar section), northern Iran, has been studied to investigate the biological and geochemical variations of this event in the eastern Tethys. Abathomphalus mayaroensis at the late Maastrichtian, Pα (Parvularugoglobigerina eugubina), P1a (Parasubbotina pseudobulloides) and P1b (Subbotina triloculinoides) at the early Danian are the recognized planktic foraminiferal biozones and subzones in the studied area. The Plummerita hantkeninoides subzone at the uppermost Maastrichtian and P0 Biozone at the base of Danian were not defined in the studied section. This proposes a short-term hiatus and sedimentary discontinuity at the base of Paleocene and probably uppermost Maastrichtian, which most likely caused by winnowing of sediments after a cooling phase and development of bottom current in the Albors Basin. The K–Pg transition in the Aboksar section is characterized by a bloom in the Guembelitria cretacea , evolution of first Danian species (Pv. eugubina , Pv. longiapertura), δ13C negative shift (about 0.5‰), and a gentle Ir anomaly (0.1 ppb). Planktic foraminifera were diverse and abundant during the late Maastrichtian of studied section in a warm (relatively lower δ18O contents) and well stratified environment. Bloom of the opportunist species, G. cretacea , and decrease of planktic foraminiferal abundance and diversity at the base of Paleocene interval propose an abnormal stressful environment in this time probably after the asteroid impact and its following temperature decline. The appearance of more complete species with more specialized shells and larger sizes, such as Globoconusa daubjergensis , Parasubbotina pseudobulloides, Eoglobigerina eobulloides and Subbotina triloculinoides in the P1a and P1b subzones and return of carbon isotope diagram into the pre-boundary values testify an environmental recovery and optimization of ecosystem conditions. • The studied interval has been deposited across the K–Pg interval of the Alborz Basin. • A short-term gap across the K/Pg boundary is marked by lack of P.hant and P0 biozones. • The base of Danian is accompanied by a gentle Ir anomaly and δ13C negative shift. • The Paleocene is initiated by planktic foraminiferal extinction and G. cretacea bloom. [ABSTRACT FROM AUTHOR]

• Five high-throughput data of ATLL were integrated and analyzed by systems biology. • The hsa-mir-146, 451, 31, and 125 might be implicated in ATLL manifestations. • Among 59 hub genes, RhoA and PRKACB had the highest decrement in ATLL patients. • The qRT-PCR in 13 ATLLs, also confirmed the decrement of RhoA and PRKACB. • Inhibition of RhoA and PRKACB as tumor suppressor are critical in the oncogenicity. Adult T-cell leukemia/lymphoma (ATLL) is a human T-cell leukemia virus (HTLV) type 1-associated disease of TCD4+ cell transformation. Despite extensive studies on ATLL development and progression, the fundamental processes of HTLV-1 oncogenicity are yet to be understood. This study aimed to integrate high-throughput microarray datasets to find novel genes involved in the mechanism of ATLL progression. For this purpose, five microarray datasets were downloaded from the Gene Expression Omnibus database and then profoundly analyzed. Differentially expressed genes and miRNAs were determined using the MetaDE package in the R software and the GEO2R web tool. The STRING database was utilized to construct the protein-protein interaction network and explore hub genes. Gene ontology and pathway enrichment analysis were carried out by employing the EnrichR web tool. Furthermore, flow cytometry was employed to assess the CD4/CD8 ratio, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm the high-throughput data analysis results. Four miRNAs, including hsa-mir-146, hsa-mir-451, hsa-mir-31, and hsa-mir-125, were among the statistically significant differentially expressed miRNAs between healthy individuals and ATLL patients. Moreover, 924 differentially expressed genes were identified between normal and ATLL samples. Further network analysis highlighted 59 hub genes mainly regulating pathways implicated in viral interferences, immunological processes, cancer, and apoptosis pathways. Among the identified hub genes, RhoA and PRKACB were most considerable in the high-throughput analysis and were further validated by qRT-PCR. The RhoA and PRKACB expression were significantly down-regulated in ATLL patients compared to asymptomatic carriers (p <0.0001 and p =0.004) and healthy subjects (p =0.043 and p =0.002). Therefore, these corresponding miRNAs and proteins could be targeted for diagnosis purposes and designing effective treatments. [ABSTRACT FROM AUTHOR]

• Ammonium Chloride led to a shorter recovery time in hospitalized patients. • Viral burden and clinical severity were lower in those receiving Ammonium Chloride. • Ammonium Chloride did not reduce the mortality rate of the COVID-19 patients. The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have antiviral effects and may be of use against SARS-CoV-2 infections. In this double-blind, single-center study, we enrolled patients with positive PCR test and/or CT findings for COVID-19. The participants of each group were randomly assigned to Diphenhydramine Compound (Diphenhydramine + Ammonium Chloride) plus standard of care or to Diphenhydramine alone and standard of care groups. The primary outcome was all-cause mortality within 30 days of randomization. Secondary outcomes include viral burden, clinical status, assessed by a 5-point ordinal scale, and length of stay in hospitalized patients. A total of 120 patients were included in the trial, 60 of which were assigned to the Ammonium Chloride group. The primary endpoint was not statistically different between the two groups (HR: 3.02 (95% CI, 0.57–16.06; p = 0.195)). Recovery time and viral burden were significantly lower in the Ammonium Chloride group, corresponding to an odds ratios of 1.8 (95% CI, 1.15–2.83; p = 0.01) and 7.90 (95% CI, 1.62–14.17; p = 0.014), respectively. The findings of this study advocate the careful addition of Ammonium Chloride to standard of care for COVID-19 patients. [ABSTRACT FROM AUTHOR]

HTLV-1 causes two life-threatening diseases: adult T-cell leukaemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. Due to the lack of proper treatment, an effective HTLV-1 vaccine is urgently needed. DNA sequences of 11–19 and 178–186 amino acids of HTLV-1-Tax and SP2 and P21 were fused to the mouse-Fcγ2a, or His-tag called tTax-tEnv:mFcγ2a and tTax-tEnv:His, respectively. These constructs were produced in Pichia pastoris , and their immunogenicity and protective properties were assessed in a mouse challenging model with an HTLV-1-MT2 cell line. The immunogenicity assessments showed significant increase in IFN-γ production in animals receiving tTax-tEnv:mFcγ2a (1537.2 ± 292.83 pg/mL) compared to tTax-tEnv:His (120.28 ± 23.9, p = 0.02). IL-12 production also increased in group receiving tTax-tEnv:mFcγ2a than tTax-tEnv:His group, (23 ± 2.6 vs 1.5 ± 0.6, p = 0.01), respectively. The IFN-γ and IL-12 levels in the Fc-immunised group were negatively correlated with PVL (R = -0.82, p < 0.04) and (R = -0.87, p = 0.05), respectively. While, IL-4 was increased by tTax-tEnv:His (21.16 ± 1.76 pg/mL) compared to tTax-tEnv:mFcγ2a (13.7 ± 1.49, p = 0.019) with a negative significant correlation to PVL (R = -0.95, p = 0.001). The mouse challenging assay with tTax-tEnv:mFcγ2a showed 50 % complete protection and a 50 % low level of HTLV-1-PVL compared to the positive control receiving HTLV-1-MT2 (p = 0.001). Challenging experiments for the His-tag protein showed the same outcome (p = 0.002) but by different mechanisms. The Fc-fusion construct induced more robust Th1, and His-tag protein shifted more to Th2 immune responses. Therefore, inducing both T helper responses, but a Th1/Th2 balance in favour of Th1 might be necessary for appropriate protection against HTLV-1 infection, spreading via cell-to-cell contact manner. [ABSTRACT FROM AUTHOR]

Abstract: Background: Stroke is the third common cause of mortality and the most common cause of morbidity in adults. MLC601 (NeuroAiD™) is a treatment indicated for post stroke recovery. An increase of impaired cerebral blood flow may be an important parameter for recovery processes. The aim of this study was to investigate the effect of MLC601 on cerebral blood flow velocity as an indirect evidence of cerebral blood flow increase in post stroke subjects. Methods: This is a double-blinded, placebo controlled, randomized study of 80 subjects included within a week of stroke onset. All subjects were given either MLC601 or placebo, 4 capsules, 3 times a day for 3 months. Cerebral blood flow within the middle cerebral artery, with blood flow velocity measured by transcranial Doppler (TCD), and Barthel index was assessed at baseline and at 3 months. Results: The mean change in cerebral blood flow velocity in the MLC601 treatment group (15.9) was significantly increased (p =0.009) compared to the placebo group (9.6). Subjects in the treatment group also showed a significant difference in the mean rank of modified ranking scale (p <0.001) and mean change of the Barthel Index: 36 vs. 29 in the placebo group (p <0.001). Conclusion: This is the first study suggesting that treatment with MLC601 may increase cerebral blood flow in stroke subjects. This may be mediated by an effect on stimulating microcirculation, an important process contributing to neuroplasticity in the central nervous system. This effect on cerebral blood flow may be associated with improvement in measures of functional recovery. [Copyright &y& Elsevier]

Human T-lymphotropic virus type-1 (HTLV-1) is a retrovirus that causes the neurological disorder HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP) and/or adult T-cell leukemia/lymphoma (ATLL). Iran is one of the endemic regions of the HTLV-1 in the Middle East. To infer the origin of the virus in Iran and to follow the movements of human population and routes of virus spread to this country, phylogenetic and phylodynamic analyses were performed. To this purpose, the long terminal repeat (LTR) region of HTLV-1 was used. New LTR sequences were obtained from 100 blood samples which infected with HTLV-1. Moreover, all Iranian LTR sequences which have been reported so far, were obtained from GenBank database. Sequences were aligned and maximum-likelihood and Bayesian tree topologies were explored. After identification of Iranian specific cluster, molecular-clock and coalescent models were used to estimate time to the most recent common ancestor (tMRCA). Bayesian Skyline Plots (BSP), representing population dynamics HTLV-1 strains back to the MRCA, were estimated using BEAST software. Phylogenetic analysis demonstrated that the Iranian, Kuwaiti, German, Israelite and southern Indian isolates are located within the widespread "transcontinental" subgroup A clade of HTLV-1 Cosmopolitan subtype a. Molecular clock analysis of the Iranian cluster dated back their respective tMRCA to be 1290 AC with a 95% HPD confidence intervals (918, 1517). BSPs indicated a rapid exponential growth rate in the effective number of infections prior the 15th century. Our results support the hypothesis of a multiple introductions of HTLV-1 into Iran with the majority of introductions occurring in prior the 15th century, at the same time the Mongol invasion of Iran. Our results further suggest that HTLV-1 introduction into Iran was facilitated by the commercial/migratory linkage as known as the ancient Silk Road which linked China to Antioch (now in Turkey). • Phylogenetic and dynamic studies demonstrated the origin, movements of human population, and spread routes of HTLV-1 in Iran. • The Iranian, Kuwaiti, German, Israelite and Indian isolates are belonging to HTLV-1 Cosmopolitan subtype, transcontinental A. • Primary spreading of HTLV-1 into Iran might be occurred prior to the 15th century, the time of Mongol invasion to Iran. • Spreading of HTLV-1 in Iran could be facilitated by the commercial/migratory linkage via the ancient Silk Road. [ABSTRACT FROM AUTHOR]